CT-defined sarcopenia and outcomes in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors

Abstract

Sarcopenia is increasingly recognized as a potential prognostic factor in patients with cancer, but its clinical significance in HR+/HER2− metastatic breast cancer treated with CDK4/6 inhibitors remains uncertain. This study investigated the association between CT-defined sarcopenia and clinical outcomes in this population. This retrospective multicenter study included 94 patients with HR+/HER2− metastatic breast cancer who received ribociclib or palbociclib plus endocrine therapy between January 2021 and March 2024. Baseline sarcopenia was defined using the skeletal muscle index measured on CT at the third lumbar vertebral level (L3). Progression-free survival (PFS) was estimated using the Kaplan–Meier method. Cox proportional hazards regression was used to identify prognostic factors for PFS, with CT-defined sarcopenia, continuous skeletal muscle index (SMI), and total muscle area (TMA) evaluated in separate multivariable models. CT-defined sarcopenia was present in 37 patients (39.4%). Median PFS was markedly shorter in patients with sarcopenia than in those without sarcopenia (15.2 vs. 26.6 months; log-rank p  < 0.001). At 1 and 2 years, PFS rates were 57.6% and 15.2% in patients with sarcopenia versus 84.1% and 56.0% in those without sarcopenia, respectively. In separate multivariable models, CT-defined sarcopenia remained independently associated with shorter PFS (HR, 3.22; 95% CI, 1.86–5.59; p  < 0.001), whereas higher continuous SMI (HR, 0.93; 95% CI, 0.89–0.97; p  = 0.001) and TMA (HR, 0.97; 95% CI, 0.96–0.99; p  = 0.002) were independently associated with longer PFS. Higher Ki-67 expression and second-line CDK4/6 inhibitor therapy also remained significantly associated with shorter PFS across all three models. CT-defined sarcopenia was an independent prognostic factor of inferior PFS in patients with HR+/HER2− metastatic breast cancer receiving CDK4/6 inhibitor-based therapy. Assessment of skeletal muscle mass on routinely acquired baseline CT scans may offer a practical tool for risk stratification and may help identify patients requiring more intensive follow-up and supportive care.